The purpose of this study is to assess the effects of pre- and postnatal exposure to the organophosphorus (OP) pesticide chlorpyrifos (CPF) on neurobehavioral functioning in a cohort of inner-city children who have reached 9 years of age. This work builds on, and shares a cohort with, a prospective cohort study of ambient air pollutant effects on child development and respiratory health, being conducted by the Columbia Center for Children's Environmental Health (NIEHS R01 ES08977, P.I. Perera:11/01/03-10/31/08; 5 P01 ES09600/EPA RD-83214101, P.I. Perera, Co-I Rauh:11/01/03-10/31/08). Previous findings from the Children's Center study reveal adverse effects of prenatal exposure to CPF (validated with biomarkers in cord blood) on birth weight (Whyatt et al., 2004), cognitive and motor development, and neuro-behavioral problems at 3 years (Rauh et al., 2006). Affected neurobehavioral areas include attention and ADHD-- conditions with serious long-term clinical implications. Based on these findings, and evidence from the experimental literature showing long-term, possibly irreversible effects of CPF exposure on brain development and sensorimotor activity (Dam et al, 2000; Levin et al, 2002; Slotkin et al, 2005), we now propose to evaluate the longer-term neurodevelopmental effects of CPF in 300 9-year-old children. We will use Magnetic Resonance Imaging (MRI) to define the intermediary neurobiological effects of CPF exposure on the structure, metabolism, and anatomical connectivity of the brain in all 300 children. CPF was selected as a model for translational research because it is representative of the class of OP pesticides, well characterized, and well-studied in animals. Furthermore, agricultural and commercial uses continue, despite the 2001 residential ban by EPA. Specifically, we propose to: (1) assess the 9- year effects of prenatal and early childhood exposures to CPF on neurobehavioral (inattention, hyperactivity and depression) and neuropsychological functioning (attentional capacity, memory, impulse control and sensory motor functioning); and (2) assess the 9-year effects of prenatal and early childhood exposures to CPF on measures of brain structure (using anatomical MRI), brain chemistry/cellular metabolism (using magnetic resonance spectroscopy), and anatomical connectivity (using diffusion tensor imaging) in the same children. PUBLIC HEALTH RELEVANCE: This application is for a 5-year study to assess the effects of exposure to the organophosphorus pesticides, chlorpyrifos and diazinon, on neurobehavioral functioning in a cohort of inner-city children (n=400) who have reached 8-9 years of age. This work shares a cohort with a longitudinal study of ambient air pollutant effects on child development, from the prenatal period to 9 years of age, being conducted by the Columbia Center for Children's Environmental Health. The project has access to biomarkers of exposure, includes neuroimaging assessments on a subset of 60 children, and has potential for further informing regulatory safety standards for OP use in the United States.